Antibody discovery

Multi-pass transmembrane proteins address a serious challenge as they are difficult to purify in their native 3D-structure. Icosagen has engineered a platform to specifically tackle diverse membrane-associated antigen classes, such as GPCRs. To overcome purification complexities with multi-pass transmembrane proteins, we utilize virus-like particles (VLPs) to effectively purify complex proteins in their native 3D-structure. Subsequently, these VLPs serve as a valuable tool for immunization in membrane protein antibody discovery projects.

Read more about immunization and membrane protein expression. 

Antibodies, aslo known as immunoglobulins (Ig), are large Y shaped molecules divided into five primary isotypes: IgG, IgM, IgA, IgD and IgE. They are produced by the immune system in response to the presence of foreign substances, know as antigens. Antibodies circulate in the blood and provide a specific defence mechanism against infections and diseases. Some of the key functions of antibodies are neutralization, opsonization, complement activation, antibody-dependent cellular cytotoxicity (ADCC) by recognizing foreing substances, via neutralization, phagocytosis.

Antibodies consist of two heavy and two light chains. The heavy chain defines the isotype of an antibody (IgG, IgM, IgA, IgD and IgE), whereas the light chains are classified as kappa or lambda. Variable regions of both heavy and light chain are responsible for the crucial step in the immune response – binding to the target antigen.

Polyclonal antibodies differ from monoclonal antibodies, because they are produced by many different B-lymphocytes, and therefore identify a different epitope on an antigen. On the contrary, monoclonal antibodies are derived from single B-cell clone and identify a single epitope.

Antibodies serve as valuable tools in drug discovery, aiding in target identification, validation, characterization and the development of antibody-based therapeutics. Their high specifity, ability to bind diverse targets, long half-life and versatility in enginereing, makes them highly valuable as therapetics. 

Our expertise covers discovery, development, and manufacturing of mammalian therapeutic antibodies up to clinical candidate development, including stable CHO cell line development for GMP manufacturing. 

A chimeric monoclonal antibody is an engineered antibody that combines the variable domain of an antibody from one host species (e.g. chicken, rabbit, llama, etc.) with the constant domain of an antibody from different species (e.g. human). Although, these structural chimeras were first created to minimize human anti-mouse antibody (HAMA) response, humanized antibodies are distinct from chimeric antibodies as they carry a larger stretch of sequences from human antibodies. And therefore, having a lower immunogenicity, humanized antibodies are used as immunotherapeutic agents. 

Our humanization platform allows us to routinely humanize antibody variable regions from the light (VL) and heavy chains (VH) from any species. Read more about humanization service. 

We have the versatility to employ individual or combined approaches, utilizing both in vivo and in vitro methods. This spans from B-cell cloning to the creation of fully synthetic phage libraries to yield specific, high affinity antibodies for any target class. Our experienced antibody discovery team will choose the best approach, tailored for specific molecule, whether it is simple IgG or more complex integral membrane protein.  

The antibody discovery workflow begins with target identification and validation, followed by the immunization of a host animal with the antigen. For the discovery, to isolate desired antibodies with high affinity and specificity, we use B-cell panning and hyperimmune or synthetic phage libraries for screening. The selected antibodies undergo transient production and are characterized for binding kinetics, specificity, and functionality. Lead engineering and optimization are implemented to enhance properties such as affinity and humanization, to name a few. 

A good therapeutic antibody can be determined by studying the affinity, specificity, purity, cross-reactivity and most importantly its intended function. While the first three can be analyzed using a well-equipped machinery park, cross-reactivity and functional analysis require in vivo assays. Final confirmations of the antibody  emerge at the end of clinical trials.

We offer end-to-end services for bi- and multispecific antibodies, handling everything from discovery and engineering to production. Our tailored analytics and purification processes ensure each molecule meets set requirements. Alternatively, to design and production of bispecific antibodies, we can produce and purify antibodies directly from electronic sequences provided by our customers. 

Read more about bispecific antibody production and bispecific antibody engineering. 

Our distinctiveness is the CRDMO concept, that lies in serving as a one-stop-shop for biopharmaceutical, biotechnology and diagnostic sectors. This encompasses our full expertise, spanning the entire spectrum from discovery and development to manufacturing of mammalian therapeutic antibodies.
Several antibodies, discovered and manufactured for our customers, are used in clinical diagnostics or in clinical trials.
In 2024, Icosagen’s on-site GMP facility will be completed, opening up additional capabilities for producing therapeutic antibodies and proteins for clinical trials. This is where the scientist together with the cutting-edge technology converge, to create science that reaches people.